Long COVID is real, but may be overestimated (Patreon)

[This is a transcript with links to references.]

Remember COVID? It’s over, right? Except for some people it isn’t over, and maybe it never will be. Estimates say that as much as one in 10 people who had COVID were still affected more than 3 months later. They got long COVID.

But what’s long COVID? What might cause it, how common is it, and what should you do if you think you’re affected? That’s what we’ll talk about today.

First things first, what’s long COVID? Long COVID isn’t a single disease, it’s a collection of symptoms. In the scientific literature it goes under the name “Post-COVID conditions” or “post-acute sequalae of COVID”.

Seque-what? Sequelae, as everyone knows after looking it up on Google, is the plural of sequela, that’s “a condition which is the consequence of a previous disease or injury”. I can see this becoming a very popular girl’s name.

Ok, so long COVID is basically the aftermath of COVID. If you want a more accurate definition, the World Health Organization defines long COVID as the “continuation or development of new symptoms three months after the initial COVID infection, with these symptoms lasting for at least two months with no other explanation.”

Long COVID includes more than 200 symptoms. The most common one is brain fog, that’s a catch-all for cognitive problems, such as impaired attention, problems concentrating, difficulties with memory, processing speed, and executive function. Basically, brain fog means that your brain wafts slowly through the forest.

Other common symptoms are extreme fatigue and exhaustion, general weakness, abnormally fast or strong heartbeats, difficulty breathing, and reduced mobility. The symptoms may start soon after infection or sometime after recovery from the infection.

Some conditions brought on by long COVID had been known previously, notably myalgic encephalomyelitis. Since no one can pronounce that, it’s also known as ME, chronic fatigue syndrome, or ME/CFS for short.

Another condition associated with long COVID goes under the name of dysautonomia, that’s problems with the autonomic nervous system. That’s the system which controls involuntary bodily functions like heartbeat, breathing, digestion, and cracking stupid jokes.,

Dysautonomia includes in particular what’s called postural orthostatic tachycardia syndrome, that’s an abnormally high heart rate when standing. Both ME/CFS and dysautonomia are commonly seen in patients with long COVID.

Constantly feeling tired and exhausted sounds like a pretty common condition, especially if you have children, but the tiredness of long COVID and chronic fatigue syndrome is not your everyday tiredness.

Patients who suffer from it literally seem not to produce enough energy to stay alert and mobile. If they move too much or do anything really, they suffer “crashes” after which they might be barely able to move or think for days or weeks.

The exact causes are subject of research but in a paper from August this year ,a large international group of researchers put forward evidence that COVID can cause a dysfunction of mitochondria. Mitochondria are parts of cells which can create energy from chemical reactions. They found this by doing autopsies on 35 people who died from covid and found that mitochondrial function had recovered in the lung, but had remained impaired in the heart, kidney, liver, and lymph nodes.

This isn’t the only physical damage that COVID has been found to cause. In a recent paper a group of American neurologists report that long COVID suffers have abnormalities in blood samples and the cerebrospinal fluid, that’s a fluid inside the brain. Other studies have found that the gut microbiome is significantly altered.

There are also several studies that compared the brain functions of long COVID patients to control groups and found that they are significantly altered. For example, in a Nature paper from last year,  a group from the UK used MRI to study the brain activity of long COVID sufferers and among other things that the brain size was reduced by roughly 0.3 percent .

So scientists have found a bunch of physical changes associated with long COVID. They still don’t know what causes these changes, but they believe there are multiple contributing factors.

Besides the mitochondrial dysfunction that affects energy generation in cells, another hypothesis is that it could be caused by reservoirs of COVID viruses in tissues, problems with regulating the immune system, changes in gut bacteria, tiny blood clots, suboptimal signaling in the brainstem.

Scientists also believe that the reason long COVID so often has neurological effects is that the brain happens to be very close to the nose which, if nothing else, is at least an argument that I can follow.

In some sense the public attention that long COVID has received has been a blessing for people who suffered from chronic fatigue syndrome already prior to COVID. Now at least they’re being taken seriously.

Trouble getting taken seriously is an issue especially for chronic diseases that don’t yet have a consensus definition, standard test, or diagnosis. It’s something you can’t have because there’s no box to check. In these cases, patients all too often get told they don’t really have problem or it’s a psychological problem or stress or whatever. There’s even a term for it: “medical gaslighting”.

“Gaslighting” is one of the obscurer newcomers in the English dictionary. It derives from the 1944 movie Gaslight, in which a man makes his rich wife think she’s insane, so he gets a grip on her inherited jewelry. He does it by manipulating the gas lights without telling her, then insisting she’s imagining it, hence the name.

The term “gaslighting” is now broadly used for questioning someone else’s experiences. Medical gaslighting happens when doctors dismiss or downplay symptoms of patients.

A 2006 article by a scientist at MIT aptly called these conditions ‘‘illnesses you have to fight to get’’ because health insurances have an interest in denying the reality of chronic illnesses. This has included and continues to include chronic fatigue syndrome, migraine, fibromyalgia, and chemical sensitivity.

And it seems to be happening for long COVID too. In 2022, a group of researchers in the United States asked more than 300 long COVID patients about their experience with getting treatments.

79 percent reported negative interactions with medical professionals, and 34 percent said their problems were dismissed by doctors, among other things as anxiety and depression, women’s troubles, and psychosomatic. Unfortunately, they didn’t have a control group and for all I know, it’s totally normal for 79 percent of patients to have issues with medical professionals.

Okay, so long COVID is a real thing and it is very unpleasant, but how common is it? More common than you might think. According to data from the American Center for Disease Control, more than 15 percent of American adults have, or have had, long COVID, and almost 6 percent still have it today.

This means that in the United States alone, there are more than 23 million people who have long COVID. An article from earlier this year estimates that globally at least 65 million people have it. And the numbers are rising.

However, not all of those people are severely affected. According to the CDC, it’s “only” about a quarter of long COVID patients who are severely affected, though that’s still one to two percent of all adults.

But these numbers are somewhat controversial. In a recent article that appeared in the British Medical Journal, a group of scientists complained that the long COVID diagnosis is “overly broad”, and because of this, the numbers of those affected are vast overestimates. Indeed, the list of supposed long COVID symptoms keeps getting longer and longer with two recent additions being hair loss and sexual dysfunction.

The authors of the new paper say the problem is that most of the existing long COVID studies have methodological problems. For example, almost half of those studies didn’t confirm that the enrolled participants had a COVID infection in the first place. And almost 90 percent of them didn’t have control groups. That’s problematic, because if you have a list with 200 symptoms, the chance that randomly picked people will have one or the other symptom is is pretty high.

If you look at a study with a control group, like this one,  you’ll see that people who never had COVID report one or the other long COVID symptom 3 to 4 percent of the time. Among those who had COVID, there are more who have those symptoms 20 weeks after infection, but it’s not such a huge difference.

The researchers say that the estimate that 6% of adults suffering from long COVID is incorrect and it’s more like 1%. That’s very comparable to the estimate from the CDC for the fraction of people who is severely affected. And if you ask me, I think one in a hundred is still a pretty high number.

So now we know how many people it has, who has it?

Not everyone has the same risk of getting long COVID. Data reveal that those in middle age are affected more often than the youngest and oldest. And women are much more likely to get it than men. Of adult men in the United States about 11 percent got long covid, whereas for women it was about 18 percent.  

Among middle aged women the ratio is then as high as 23%. This is maybe not so surprising, seeing that women generally suffer more often from autoimmune problems and are more than twice as likely as men to get chronic fatigue syndrome.

Demographic factors matter too. Black people in the United States are affected twice as often as American Asians. Among trans people the ratio is as high as 20 percent. It’s probably not that COVID viruses particularly like black or trans people, but rather that being a member of those demographic groups is correlated with other factors, such as living in big cities or in difficult economic circumstances, stress, lack of access to healthcare, and so on.

The data have also revealed pre-existing conditions that increase the risk of getting long Covid, in particular that’s type 2 diabetes, some types of allergies, and a few other conditions. But a third of people with long COVID had no identified pre-existing conditions.

How long is long COVID? Hard to say since COVID itself has only been around for 4 years. Yes, it’s only been four years!

So, we know that it can last up to four years… but quite possibly even longer. This is because doctors know that chronic fatigue syndrome and dysautonomia is often lifelong. Fortunately, while long COVID symptoms might remain for a lifetime, several studies have found that in most cases they do at least improve.

For example, just a few months ago a team of researchers from the US published a paper  with results from a study in which they followed almost 140 thousand people who had COVID and a control group of almost 6 million people. So that’s a really big study.

They tracked the prevalence of symptoms such as fatigue, diabetes, dizziness, and so on and found that among people who had not been hospitalized for COVID, 69% of the symptoms were no longer significant two years after infection. For those who were hospitalized, that percentage was only 35 percent.

To medical professionals the idea that virus infections cause long-term damage isn’t new.

For example, it’s been found previously that people born during the 1918 influence pandemic have a 2-3 times higher risk of Parkinson's disease. There’s also the post-polio syndrome which usually occurs a few decades after infection and causes a progressive weakening of the muscles and fatigue. And a review which appeared earlier this year lists 45 cases where virus exposure has been found associated with increased risk of neurodegenerative diseases, such as Alzheimer or Parkinson.

Ok, clearly you don’t want to have long COVID. How can you avoid it? The best way of not getting long COVID is not getting COVID in the first place. So, you know, move into a hut in the desert or something.

If that’s not an option, get vaccinated because that reduces the risk of getting long COVID. According to a meta-review which just appeared in October, two vaccinations reduce the risk of getting long COVID after an infection by roughly 37 percent, three by 69 percent. But only if you get vaccinated *before catching COVID.

If you already had COVID, avoid getting it again, because if you didn’t get long COVID the first time you can still get it the second time. It’s unclear whether the risk is higher or lower the second time, because there are two opposing factors. One is that the second time the body has seen the virus before and knows how to deal with it. On the other hand, if you have symptoms caused by an overreaction of the autoimmune system, that might actually be worse the second time around. Either way, the cumulative risk can only go up, so try to avoid additional viruses.

If you do get COVID, doctors say it’s important that you rest well and don’t try to push through it because that increases the risk that you’ll never fully recover.

If you watch this video because you have long COVID or think you might have long COVID, first of all, I wish you well and hope you do get better.

Second, both the American CDC and the European CDC recommend that if you think you have long COVID, you should make a list of your symptoms and note down how often they occur, what makes them worse, and how much your life is affected. Then you should go and see a health care provider with your well-prepared list and they’ll surely be impressed.

What do you have to expect for treatment? The current recommendation is that first you take antivirals just to make sure there’s no COVIDs hiding away in some corner. The next step depends on exactly what seems to cause your troubles. If it seems to be an overactive immune system you can take a class of drugs called “immuno-modulators”. If you have blood clots, you take a drug for that, if it’s mostly neurological issues, you get drugs targeting those, and so on. So it’s not a one-size fits all approach, but a rather difficult treatment that needs to be tailored to the individual.

Besides looking for doctors you can look for legal, financial, and moral support online.

In the United States, there is for example the Long COVID Alliance that provides information on how to apply for benefits, housing, food, etc, and the Pandemic Legal Assistance Network, that’s a network of attorneys who have volunteered to provide free assistance to people who have been affected by COVID. In England and Wales there’s the Long Covid Supportcharity. There are many others and if I can google them, so can you.

If you know someone who has long COVID, keep in mind that in addition to the physical problems it’s psychologically difficult to cope with having your life turned upside down.

As we have seen, long COVID affects a lot of people and it’s a problem that nations worldwide are trying to grapple with.

In 2021, the US National Institute of Health invested more than 1 billion into long COVID studies. This initiative, however, has been criticized both by scientists and patients because so far only 15 percent of the funds have been used for clinical trials, and most of those just confirmed what was already known, for example that exercise makes long COVID symptoms worse.

The UK government poured some money into long COVID research in 2021, but not much has happened since. The Germans were somewhat late to the party, but just a few months ago, the German government launched an initiative to provide better care and information to long covid patients. 

In summary, long COVID is real, it really affects a lot of people, and it won’t go away any time soon. But at least the sheer number of people who are affected mean that doctors and researchers now pay more attention to chronic aftereffects of viral infections. Hopefully this means that better treatment methods will soon become available.

The quiz for this video is here.